Friday, 30 August 2013

Discussions on the various studies hinting at a possible connection between inflammation (however you wish to define this) and autism, at least some of the autisms, have cropped up with increasing frequency on this blog (see here and here). I wouldn't go so far as to say that a causal link has been established yet; as in 'inflammation causes autism', or indeed 'autism cause inflammation' but inflammation. in it's various guises, is certainly one to watch.

Amusing the muses @ Wikipedia

Outside of autism, and bearing in mind an increasingly vocal research voice suggesting common ground (see here) and connections between autism and other more psychiatrically-defined conditions such as the schizophrenia spectrum (see here), similar work also suggests a possible connection between inflammatory markers and other conditions.

Indeed today's post is dedicated to some of the cumulative work looking at schizophrenia and inflammation, and in particular one of the more reliable markers of inflammation, C-reactive protein (CRP) linked to all manner of health ills (see here for example).

I arrived at this post after reading the paper by Lin and colleagues* and their assertion that subject to much more confirmatory research being required, cases of schizophrenia which were also following a medication regime (antipsychotic meds) seemed more likely to present with elevations in CRP. The medication element to the study reflects some interest in how antipsychotics might be able to affect the CRP measure, bearing in mind the results are still fairly limited in this area (see this paper by Diaz and colleagues**).

The paper by Miller and colleagues*** provides a pretty good summary of the various research undertaken so far on CRP and schizophrenia. They concluded that there was "a 28% prevalence of an elevated CRP level in patients with schizophrenia and related disorders" and onwards quite a strong implication of increased inflammation being associated with schizophrenia. Importantly as per the autism example, this does not necessarily mean that inflammation is causative of schizophrenia or vice-versa.

It is noteworthy that a name which has appeared more than once on this blog has also thrown their research hat into the schizophrenia-CRP arena. Faith Dickerson (with a mention for Robert Yolken too), famous around these parts for her various studies on schizophrenia with the gondii in mind (see here) and a few other potential important associations (see here), also suggested that CRP levels tended to be on the higher side in cases of schizophrenia****. They reported that even after adjusting for various potentially modifying variables such as smoking status (see here) and body mass index (BMI) (see here), CRP levels were elevated in their participants with schizophrenia above and beyond asymptomatic controls and even those diagnosed with bipolar disorder. That bipolar disorder bit has also been explored a little bit more with CRP in mind too*****.

Importantly Dickerson and the other authors included in this mini-review post highlight how elevated CRP outside of any direct connection with either the onset or perpetuation of schizophrenia might place a person at enhanced risk of various health-related issues (see here). Without wishing to sound too morbid, heart health in schizophrenia for example, does not seem to have a great track record as per some previous discussions on this blog (see here). That finding perhaps as part of a greater package of issues with physical health screening and mental illness (see this paper from Barley and colleagues******) and some inequality which appears to be present.

Just before I go, I wonder if it would be worth mentioning a few other potential points of interest which perhaps require some further investigation. I touched upon the topic of homocysteine - the big 'H' - and schizophrenia in a previous post (see here) and also an intersecting area dealing with folate metabolism (see here). Homocysteine, whilst still the topic of some debate, was at one time talked about with issues related to things like cardiovascular health (see this paper by Wald and colleagues*******). Appreciating that humans are very complex creatures and sweeping generalisations about one compound = risk of one disease seem to serve little use, one might choose to enquire whether CRP levels might correlate with homocysteine and whether this clarifies any health-related relationship or not? Something along the lines of this paper but with larger participant numbers and without the interfering variables. Indeed as per another Dickerson paper******** whether CRP plus [insert variable of your choice here] might provide further insights into how CRP levels could even affect some of the facets of schizophrenia itself.

I've talked about the other strands of NICE guidance for autism before on this blog, covering pathways to diagnosis and autism in adulthood including the issue of medication and core symptoms. To recap: here in the UK, NICE are charged with providing the evidence-based clinical guidance on what does and doesn't work for diagnosing and managing all manner of health-related conditions.

With autism in mind, NICE were charged with trying to make some sense of the myriad of research results produced on the topic of autism, and offer something like a coherent set of national standards for autism; in particular focused on the core symptoms of autism. Not an easy task when faced with such a heterogeneous diagnosis complicated by all manner of possible comorbidities.

So what does the guidance suggest?

Well, despite covering a sizeable proportion of all manner of autism intervention and management strategies, the message is a familiar one: a dearth of authoritative data on what might and might not work but social-communication strategies offer probably the best option including focusing on joint attention.

I'm very pleased to say that throughout the document is recognition of the fact that autism can and does present alongside comorbidity and such comorbidity can affect symptoms including the so-called challenging behaviours.

Anxiety receives some welcome attention, although I'm slightly hesitant to endorse the suggestion that CBT (cognitive behavioural therapy) should be the preferred route of tackling such anxiety. Talking therapy might very well have some effect for some people, but as per the study by Mazurek and colleagues (see this post), there's still a gap in the knowledge base about the role that anxiety plays when it comes to autism.

I'm sure that some people will have picked up the guidance that neither antipsychotics, antidepressants or anticonvulsants should be used to manage the core symptoms of autism similar to the adult guidance.

Transition from child to adult services also gets a mention. Alongside the changes in things like SEN provision, one would hope that the cliff-edge that is post-16 provision should turn into more of step rather than a void.

What's missing from the guidance? Well in my view, whilst discussion is made of trials such as one by Jim Adams and colleagues on vitamin supplementation (see here) and the early work being reported on things like NAC (see here), none of these areas figure in the final summary guidance. There also appears to be no mention of the various amino acid, immunological or other biologically-mediated findings which is rather disappointing. That for example autism (sorry, the autisms) might also results from issues with branched-chain amino acids (see here) or PKU (see here) are important points; more so when you consider that simple interventions might actually be able to impact on symptom presentation. And then there is the whole mitochondrial story, everyone's favourite scrabble classic MTHFR and its link to folinic acid, vitamin B12, tetrahydrobiopterin (BH4)... the list goes on.

Appreciating that the evidence base around lots of areas in autism is still in its infancy, I take heart that NICE have cast an eye over autism and various facets of its presentation. That also it provides a roadmap for where research should be looking more closely is something else to take from the guidance and its potential ability to direct research funding into priority areas.

I know that this research area is still a little bit of a hot potato when it comes to a heterogeneous, behaviourally-defined condition like autism (sorry, the autisms). As I intimated in a previous article about some related study in this area (see the ClinicalTrials.gov entry here) there are still quite a lot of unanswered questions about whether stem cell therapy is 'right' for autism or not; the progress of which is not helped by the historical propagation of the therapy via all those Google ads for specialist clinics offering stem cell services.

The new paper is open-access and includes a notable addition to the authorship group - one Paul Ashwood from UC Davis who has appeared more than once on this blog - and basically reports the results of a trial investigating "the safety and efficacy of combined transplantation of human cord blood mononuclear cells (CBMNCs) and umbilical cord-derived mesenchymal stem cells (UCMSCs) in treating children with autism". Without trying to rehash the authors findings, they basically suggested that (a) aside from some cases of transient fever, stem cell therapy was relatively 'safe' when it came to the monitoring of various measures, at least over the course of the investigative period and (b) compared with a control group who only received "professional sensory integration and behavioral rehabilitation therapy", two other groups of children who received CBNMC and CBMC + UCMSC transplantation in addition to behavioural intervention showed various "improvements" according to the behavioural measures used over the course of the 24 week trial. Indeed, the combination therapies CBMC + UCMSC transplantation "showed larger therapeutic effects than the CBMNC transplantation alone". That being said, this was quite a small trial and the trial was non-blinded and non-randomised.

I'm going to reiterate my oft-cited caveat about this blog not giving medical or clinical advice particularly when it comes to something as 'new' as stem cell therapy being suggested for autism. I am inclined to point you towards another archive post where stem cell transplants were mentioned with autism (or at least mouse models of autism) in mind, based on the impressive work coming out of Paul Patterson's laboratory (see here) and how immune function, development and behaviour might be players at the same table for some cases of autism. The more recent paper has gone beyond mouse models....

Every therapeutic option which is put forward for 'managing' the characteristics of autism needs to start somewhere when it comes to testing for safety and efficacy and stem cell therapy is no exception. Whilst questions still remain about the long-term safety and effects of such transplantations and indeed, whether there is any appetite for such an intervention, the research toe has well and truly been dipped into the experimental waters.

Indeed, when reading the Wikipedia entry for how the valganciclovir - lets call it VGCV to save my poor typing hands - trial was long awaited on the back of some rather more preliminary observations (see here** and here***), one gets the idea that the recent Montoya paper might eventually turn out to be something pretty important. That being said, I'm going to turn to my old caveat on this blog about not providing medical or clinical advice.

They found a few differences between VGCV and placebo in their group, some of them significant and some of them not so. Importantly - long quote coming up - "statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P=0.039), FSS score (P=0.006), and cognitive function (P=0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months." Interesting too that among the biological results there were signs of a shift in immune function towards Th1 in the VGCV group (see here for a description) among other things.

OK, a couple of steps back first. This was a study based on quite a well-defined group of people with CFS who also presented with signs of an immune response (IgG antibodies) against human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV). I understand that these viruses or rather exposure to these viruses have been discussed with CFS in mind previously (see here**** and here***** for example) outside of the historical viral reference (PVFS) although there still remains some 'discussion' about their role and relationship to CFS if and when detected.

I appreciate that to some, viral infections and CFS is still a little bit of a thorny issue in light of the quite recent XMRV story (see here for the drama) and even earlier some chatter about the use of transfer factor********. There is, therefore, always the possibility that the latest Montoya research might unfortunately suffer a sort of death by association as a consequence of any perceived link, despite the fact that as far as I can see they steered clear of anything murine leukemia virus-related virus in their work. Indeed as an aside, I should also point out the very interesting work being done on HERVs and myalgic encephalomyelitis (ME) which may or may not be relevant to the Montoya investigation too.

Friday, 23 August 2013

It is a question that I'd imagine most paediatricians or related healthcare professionals get asked a lot when it comes to the autism spectrum conditions: "my child has autism, what is the risk that any future siblings might also develop the condition?"

OK, I know that this is not new news. That more than one child in the same family might have autism is a reality that many, many families have experienced. Science has been talking a long time about the heritability of autism (and the broader phenotype) from quite a few perspectives; even though genes are probably not working in isolation (see this archive post) alongside that new Sheriff in town called epigenetics (see here). Another important issue taken up from this recent paper outside of the disparity between this population-based study and other more clinical samples - the estimates from the Grønborg paper are lower than that found in other studies - is how those just-as-important half siblings seem to indicate other potential issues also being pertinent areas for further investigation (think the nine months that made us and things like folate even the folding placenta for example).

There is always a need for this kind of basic science in autism circles not only for research purposes but also to inform families about risk (bearing in mind that risk is risk) and potentially inform services such as education and health as a function of things like heightened comorbidity too (see here). Indeed if I had to add anything to this area of investigation it would be to include autism as part of a wider suite of conditions/characteristics which may very well be noted in other siblings (see here) as per some other interesting work with its roots quite a few moons ago (see here).

With my science hat on, I was obviously interested in this research, and how despite the relatively small participant group "In each of the suicide completers, the increase in SAT1 was at least three s.d. above the average levels".

But then as I read the words again, the realisation set in that these 'completers' were not just mice or rats in a cage, they were people. People who only 24 hours prior to their inclusion in the study were alive. And then for whatever reasons decided to end their life and with it the hopes and dreams of their parents, siblings, partners, extended family and friends.

Don't get me wrong, I'm not saying that we shouldn't be actively engaging in research looking at how we might eventually predict those at greatest risk from suicide. On the contrary, if this work pans out and survives replication the potential savings both in terms of that most precious commodity (life) and beyond could be enormous. But it is still an 'if' and those were real people.

The Le-Niculescu paper is open-access so I'm not going to go through it with a fine-toothed comb on this occasions. Suffice to say that this study, following previous interest from this authorship group (see here), set out to explore whether it was possible to predict and track suicidal states, particularly in those at high-risk for suicide as per their selection of participants diagnosed with "a major mood disorder (bipolar disorder)".

This involved first looking at blood gene expression in participants focused specifically on those who "switched from having no suicidal thoughts to scoring highly on a suicide-risk scale". The myriad of data this generated was then subject to analysis via an author favourite technique called Convergent Functional Genomics (see here**) used "to identify and prioritize from the list of differentially expressed gene biomarkers of relevance to suicidality". It was then a process of checking the top ranking gene biomarkers in those suicide completers (drawn from a different population) and "Niculescu's team was left with six which they was reasonably confident were indicative of suicide risk". More boiling down of the biomarkers was accomplished by looking at a further group of those hospitalised for suicide (attempts) and "SAT1, PTEN, MARCKS and MAP3K3 might be not only state biomarkers but trait biomarkers as well".

In all the chatter about this study, one particular question was floating around my mind: if these biomarkers are verified, does this mean we could eventually affect gene or biochemistry and somehow alter the behaviour of those attempting or thinking of attempting suicide?

Actually the authors do mention some potentially important information about this. They report for example, that the drug clozapine might affect expression of some of the biomarkers "in opposite direction to our human suicidality data in previous independent animal model pharmacogenomics studies conducted by us". Clozapine as they note is indicated for suicidality under certain circumstances (see here). Fair enough, an antipsychotic might help, bearing in mind it is an antipsychotic and carries some of the usual side-effects (see here).

But they also mention another possibility that requires some further study, as per this quite long quote:

"Several of the biomarkers from our current study (SAT1, S100A8, IL1B and 16 others) were changed in expression by omega-3 treatment in the blood of the circadian clock gene DBP (D-box binding protein) knock-out mouse model in opposite direction to our human suicidality data".

So, fatty acids, particularly those of the omega-3 variety might [might!] also impact on some of those biomarkers too? This point in particular is of real interest to me and this blog. A quick trawl of the literature looking at measured fatty acids and suicidality turns up some interesting data as per studies like this one*** and this one****. I don't think anyone has convincingly said that fatty acids 'cause' suicide because suicide is a very complicated process reliant on more than just biology, but the association is an interesting one. Some recent coincidental literature on suicides in prison (see here) confirms the multi-faceted nature of suicide.

Indeed, I've talked previously on this blog about how nutrition, in many forms, has been associated with suicide risk as per the vitamin D and independently, the lithium research (see here) reported in the scientific literature. To stress again, these are associations; so one has to be cautious not to say too much at the present time about causation.

I started this post by saying how cold science is when it comes to its operation. I suppose I should end by saying that science is cold, at least in the way it is carried out and reports, because it has to be. It has to be cold and objective. Assuming that the Le-Niculescu findings are successfully replicated however, science then can start to move out of the freezer and into something rather 'warmer' approaching real-life with regards to its translation into potentially saving lives.

Tuesday, 20 August 2013

Despite knowing a little something about the discipline of psychology and in particular, it's varied success/failure (delete as appropriate) when applied to a complicated condition like autism, I'll admit that I do have some difficulty in grasping certain ideas and concepts which make up the psychological research landscape.

Before heading into the paper I should point out that this is not the first time that this type of program has been talked about with autism in mind. For example, I stumbled across this paper** by the same authorship group which talked about some potential effects from "a Shaolin-medicine-based dietary modification" which talked about removing foods which "will generate excessive internal heat and adversely affect the temper and cognitive functions" to include "ginger, garlic, green onion, spicy foods, eggs, meat, and fish". I don't really want to comment on the hows and whys of 'excessive internal heat' on autism in this post so will leave it there for now and allow readers to draw their own conclusions. I might also add that I've talked Chinese medicine and autism before on this blog as per the 'Jedi' massage (see here, lightsaber not required).

OK back to the Chan-based mind-body exercise program on self-control. The program is based on the practice of Nei Yang Gong and essentially includes "sets of slow movements that emphasize smooth, gentle, and calm movements". The authors suggest that these movement help with self-awareness and mental self-control but can also help in the reduction of stress (something all too familiar where autism is mentioned). They add that it is a slightly different program from just mindfulness and mediation. There are plenty of videos on the web illustrating the types of movements it includes.

The authors randomly allocated 46 children diagnosed with an autism spectrum condition to either the Chan-based mind-body exercise program under analysis or something called progressive muscle relaxation although only 20 kids in each trial arm completed the four-week study. Alongside measuring neuropsychological functioning, authors also ATECd the kids to pick up parent-reported behaviour changes and looked at event-related EEG results during "an inhibitory control test, namely, the Go/No-Go task".

The results: "the autistic children in the experimental group showed better self-control than those in the control group after the one-month intervention" based on the results of the neuropsychological tests. Analysis of the ATEC scores however were not so clean-cut as both groups were reported to show [variable] positive changes on the subscales (the experimental group generally however showing a more pronounced positive effect). The authors do note that when it came to looking at specific issues such as temper outbursts "the experimental group reported a significantly greater reduction" over the control group. Oh and did I mention that there were some changes on the EEG too? (bearing in mind my considerable non-expertise when it comes to this dark art).

OK, I know its tempting to look at this paper and its results and start to criticise based on things like the lack of blinding to group allocation / intervention regime and the use of the ATEC (but wait a minute...). There was also, for example, no treatment as usual group included in the study you might say. But just hold on a minute, when it comes to ascertaining medication in relation to autism and other conditions for example, on more than one occasion there has been criticism that researchers have been too over-reliant on drug vs. nothing (or placebo) over drug A vs. drug B. At least the authors in this study were able to say that their program was better than just muscle relaxation techniques. Perhaps the next study to be done would be comparing their program with something more pharmacological?

Likewise in our modern Western medical system which we all love, it is perhaps easy to rather disparagingly talk about things like 'internal heat' whilst carrying that little smirk on our faces as if 'we know better'. I don't know enough about Chinese medicine to say whether this is something real and tangible or just some ancient hand-me-down. All I can see is that the authors have made an attempt to (experimentally) bring their expertise to bear on a group of people who are probably more prone than most to issues with things like self-control and anxiety. And if it worked, well, it worked. That and I assume the fact that once one has been trained in the ways of Nei Yang Gong, it's probably going to be something that can done quite easily and certainly quite affordably in the longer term (probably also with minimum side effects I would imagine).

Saturday, 17 August 2013

NAC or N-acetlycysteine has appeared a couple of times on this blog in relation to both autism (see here) and schizophrenia (see here). Not bad for a compound which more readily finds a home in modern medicine following paracetamol (acetaminophen) overdose or as a consequence of its mucolytic properties.

As one might imagine, the autism link is of particular interest to this blog, focused specifically on the findings of Hardan and colleagues* when it came to putting NAC to the [albeit preliminary] experimental test. The results by the way were encouraging for at least some parts of the presentation of childhood autism with the promise of more to come.

As a sort of follow-up to the Hardan paper, I'm talking today about a case report offered by Ghanizadeh & Derakhshan** (open-access) highlighting a little more individual detail following the use of NAC with an 8-year old boy diagnosed with autism. I know the word 'case report' sends a shudder down many a scientific shoulder, but as I've said quite a few times before, we ignore the N=1 in autism at our peril given the wide, wide heterogeneity present and all that associated comorbidity to contend with. Real personalised medicine you might say.

If I have managed to persuade you to listen to the rest of my ramblings on this paper and topic, there are a few important points to make about/from the Ghanizadeh paper:

From the description provided, the child in question seemed quite floridly autistic with the important add-ons of hyperactivity and inattention present from an early age. Although we aren't told what exactly it means, the authors note: "His laboratory examination was unremarkable".

Indeed, the boy's nail-biting behaviours did seem to subside alongside the installation of NAC but perhaps of greater interest were the reports that "there was a marked reduction in his autism symptoms 30 days after the onset of NAC administration". OK so this report did come from the boy's parents, and without causing any offence, the issue of objectivity might come into play.

The types of 'changes' reported however were in core areas such as his verbal skills, social interaction and a quite unusual preoccupation with having his hair cut (I say unusual because a visit to the barber or hairdresser described by many parents about their child with autism, is often characterised by entirely the opposite reaction).

Aside from "a mild abdominal pain" the authors importantly say that "nothing worsened after the administration of NAC" which I take to indicate that side effects were minimal over the course of the intervention.

I should have perhaps mentioned at the beginning that there is some sound logic why NAC might have some effect on cases of autism. The amino acid cysteine as well as containing sulfur, so potentially tied into to that most forgotten areas of autism research sulfur chemistry (see here), is also the precursor to another important compound, glutathione. I know my regular readers are probably getting a little bored of me going on about this 'elephant in the room' and in particular that glutathione overview paper by Main and colleagues (see here) but a possible link is a possible link.

I was also interested to read the authors' discussions on how NAC might also have the ability to decrease "high glutamate levels". As any good biochemist will tell you, glutathione, which is dependent on cysteine, is a tripeptide which also incorporates the amino acids glycine and glutamate into its triadic manufacture. From that point of view, circumstances where any of the three amino acids were low or not optimally biologically available might affect the production of glutathione. If that happens to mean you have low cysteine levels, glutathione would be low but also this might mean levels of glutamate or glycine could be higher as a result of not being used up to make glutathione. Glutamate is another compound finding some significant interest with regards to autism and conditions presenting with autistic symptoms.

Reiterating that the Ghanizadeh paper is a case report, I do find there to be some interesting observations reported. With my speculating hat on, I do wonder whether that link with nail-biting and onwards anxiety suggested for NAC might also be part and parcel of the effect observed in this case given the quite considerable link suggested between autism and anxiety (see here)?

In recent weeks there have been some pretty exciting developments in this area, not least because of the Lau paper (see here) suggestive of some potential issues with immune reactivity to gluten - one of the food components singled out as being related to autism - to be present in some cases and potentially explanatory of why dietary intervention might be useful for some on the spectrum.

Gluten and casein KOed? @ Wikipedia

In a similar vein, I want to talk today about the paper by Laura de Magistris and colleagues*** (open-access) and their important findings reporting an increased frequency of immune reactivity to gluten and casein (the protein found in mammalian milk sources) in pediatric cases of autism following on from the Lau data.

I had mentioned this paper in a previous [mega] post on leaky gut and autism (see here). The authorship group on the de Magistris paper reads like a who's who in gluten research at the moment.

Enough of the research hero-worship, the aim of the research was to look at various facets of how children with autism handle foods containing gluten and casein from an immunological and gut permeability point of view.

The kids with autism were all fully ADOS-ed and ADI-ed to make sure that they met criteria for autism. Various other details were also collected about things like gastrointestinal (GI) history and whether or not participants were following interventions like a gluten- and casein-free (GFCF) diet. Indeed 31 participants were following - sorry "embraced" - the GFCF diet (~20%). Importantly too, among the exclusion criteria for study non-participation was a previous diagnosis of coeliac disease or inflammatory bowel disease (IBD). In other words, these were kids with autism not previously diagnosed with a serious GI complaint

Gut permeability testing revealed that about a quarter of the children with autism had "impaired intestinal barrier function" compared with about 2% of control participants (41 ASD kids vs. 1 control). As per the previous de Magistris paper, being on a GFCF diet also tended to "normalize the barrier impairment" although diet did not curb permeability altogether in comparison to the asymptomatic control group.

Anti-gliadin antibodies (IgG) were "higher in ASDs compared to controls and are not influenced by changes in intestinal permeability". Following a GFCF diet did, as one might expect, influence the presence of this immune response.

Interestingly, when it came to measuring levels of anti-deamidated gliadin peptide antibodies (IgG) the grouped values were increased in children with autism compared with controls. I'll come back to this finding shortly.

Total IgE titer levels (IgE being a marker for classical allergy) were not significantly different between the groups in line with other findings; although specific IgE antibodies to milk were reduced for those children with ASD on the GFCF diet. IgG antibodies to casein were increased in the autism group compared to controls (and again were influenced by the use of a GFCF diet).

Take my word for it, there are lots of potentially important findings here. That leaky gut (gut hyperpermeability if you wish) is a very real finding for quite a few children on the autism spectrum is important. I know for some people this might be difficult news to take in but, added to the fact that GFCF dietary intervention might abate this issue to some degree, one perhaps needs to put aside any prejudice about GI involvement in autism and whatever image(s) that conjures up and start to focus on how science can move this finding on further.

The deamidated gliadin peptide antibody finding is also particularly interesting. Basically the process of deamidation comes about when tTG (tissue transglutaminase also known as TG2) gets hold of gluten peptides and starts doing funny things to parts of their structure (see here*****). This then has knock-on effects for their relationship with antigen presenting cells of the immune system and the cascade of effects that brings to a condition like coeliac disease. The implication here is that whilst not being coeliac disease - indeed the lack of any significant HLA-DQ2/DQ8 haplotype findings in the autism group is testament to that - gluten peptides might still be acting on some cases of autism. I should mention that some involvement for tTG in relation to cases of autism has been previously discussed on this blog (see here). I hasten to add that we are not necessarily talking about the opioid-excess hypothesis and opioid peptides - not yet at least. If you want some more information about the whole coeliac disease process, you could do worse than have a look at my recent post on what we think we know about it (see here).

What these findings and that from Lau and colleagues****** (open-access) point to is a complicated picture of how dietary variables might affect biology in some cases of autism. It's a picture which contains several important elements not least potential issues with the breakdown (metabolism) of foods which contain gluten and casein (think CM-AT??), problems with the intestinal barrier and its proper function and even hints of autoimmunity as per tTG and the deamidated gluten peptide findings.

I personally think that autism research is starting to catch-up with other conditions that are being looked at with a dietary element to them such as schizophrenia and the work of Emily Severance and colleagues (see here and here) and David Niebuhr (see here). Whether there are any relationships between the findings in autism and schizophrenia is a question which perhaps needs answering, particularly in these days of common ground (see here) and spectrums overlapping (see here).

What's missing from the de Magistris paper? Well, given the authorship group in this study, I was expecting to hear something about [General] zonulin and whether or not that protein was measured and showed anything as per its other links (see here) with tight junctions in mind. That and mention of those other words bacterial translocation which seem to go hand-in-hand with leaky gut, (think Sutterella and autismfor example).

Saturday, 10 August 2013

Although now only available to subscribers, a short while back I was very peripherally involved in helping to write an article on the science of lipidomics (see here). The crux of that overview article was that the science of biological lipids - lipidomics (yes, another one of those -omics) - is really starting to make some waves when it comes to health and wellbeing. Also that one should not be too hasty in making snap judgements about fats; not all fats are equal and without them, well, none of us would be here.

Underneath the arches @ Wikipedia

As if to prove the point, I'm talking today about a paper from Paul Montgomery and colleagues* (open-access) who suggested that science might do well to take a closer look at specific types of fats in relation to childhood behaviour and cognitive performance.

Before going further into the paper and its findings, it's probably a good idea if I frame this research with a little bit of history in this area. I'm sure that some of you might already have heard about the suggestion that fatty acid supplementation, fish oils if you will, might show some link to cognitive performance in certain groups of children and in particular, the results of the Durham trial**. I know there was some 'discussion' about other angles of fish oil use here in the bracing North-East of England but I'm not going to go into that here. Suffice to say that fish oil research has not had the easiest of rides so far.

The Montgomery paper is open-access, but a few points to note:

This was a study looking at whole blood fatty acid concentrations ("broadly equating to the omega-3 index") from a fingerstick sample in just short of 500 UK children (aged 7-9 years) as part of the DOLAB study*** (open-access). DOLAB in case you didn't click on the previous link was all about seeing what happened when kids were given a DHA (docosahexaenoic acid) supplement, particularly those who were under-performing in terms of reading ability and other aspects of behaviour.

Indeed the participants included in this study were those children who were finding some difficulty with reading performance and whether their fatty acid profiles were somehow correlated with their presentation. Various psychometric measures were employed to assess things like reading ability (BAS-II) and behaviour (Conner's Rating Scales) of participants.

Results: there were quite a few bearing in mind no control group data was included in this paper so we cannot necessarily rule out a more general 'deficiency' as being present in children. Primary among them was that blood levels of the omega-3 long-chain polyunsaturated fatty acids (LC-PUFAs) which includes both DHA and EPA (eicosapentaenoic acid), cumulatively made up only an average of 2.4% of total blood fatty acids in the group studied. The authors frame this within the context of guidance for good cardiovascular health which they report should be in the optimal region of 8-12%. Quite a disparity by all accounts.

They also noted that: "blood Omega-3 LC-PUFA status in these UK children significantly predicted both their behavior and their cognitive performance". In other words, higher levels were associated with things like better reading ability and "fewer ADHD-type symptoms".

Also notable too was the link between lower blood fatty acid levels and lower reported fish intake as per reference to parental reports on their children's eating habits.

The authors conclude that because of their results "the benefits from dietary supplementation with Omega-3 LC-PUFA found for ADHD, Dyspraxia, Dyslexia, and related conditions might extend to the general school population".

Just one last thing: for any Government official who happens to tune into this blogpost, a few interesting points to mark for your attention from the study. Reading scores were correlated with socio-economic status (SES) and behaviour problems were "higher for children entitled to free school meals" (another marker of SES). Poverty it seems, might exert an effect.

I find these to be very interesting results. I know to mention that what we and our children eat might actually have some affect on cognitive and behavioural presentation is still considered controversial in some quarters, but I personally find the research base to be worthy of attention. I'm for example, taken back to the work of Bernard Gesch and colleagues**** (open-access) on nutrition and behaviour covered by Dr Emily Deans (see here) as a template for the 'diet can affect behaviour' mantra outside of more traditional medical examples. Realising at the same time, that people are complicated creatures and dietary modifications are not a cure-all for every ill.

Also that this study was 'industry-funded' is something which some might point out as being 'significant'. For me personally, the important thing was that the COI was declared as it should have been for any research on any medicine in your medicine cabinet. Indeed one might see this as even more motivation for independent follow-up of these results...?

I've covered fatty acids previously on this blog, both with an autism research perspective (see here) and also from a 'not all good news for fish oils' perspective (see here). The lessons from both these posts were that fish oil supplementation as a sort of population-wide initiative is probably not going to be the best course of action recently emphasized by that prostate cancer link (see here).

But.... that there may be specific, perhaps many specific, groups of children or young adults who either present with certain patterns of behaviour or issues with important skills like reading alongside lower circulating levels of these fatty acids, I am finding it difficult to say we shouldn't be embarking on rigourous scientific trials looking for any potential effect from such a simple intervention. Given also that the brain for example is approximately 60% fat pointing towards our fatty evolutionary heritage, there is sound logic to ensuring adequate supplies of certain types of fatty acids are present and in particular for certain groups of people***** (open-access).

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Questioning Answers

About Me

I have been involved in autism research for more years than I care to remember. My Questioning Answers blog (http://questioning-answers.blogspot.com/) is a place to describe and discuss various research into autism spectrum and related conditions. My Gutness Gracious Me blog (http://gutness-gracious-me.blogspot.com/) is for discussions on various gastrointestinal research. I make no recommendations, I am not giving any medical advice, I am not formulating any specific opinions and do not want to get into any ethical, political or religious debates. I am not trying to change anyone's opinions, views, beliefs or anything else. These are purely blogs about science and research in autism and a few other interesting things. Any posts I make are my own opinions and not reflective of any organisation I am affiliated to. Keep in mind that science deals with probabilities not absolutes.

ABOUT AUTISM SPECTRUM CONDITIONS

Autism or autism spectrum conditions describe several presentations characterised by core issues with social affect and stereotyped or repetitive actions. Diagnosis is made by observation and analysis of developmental history. These are heterogeneous conditions which can carry various co-morbidities and whilst described as life-long are affected by age and maturation. Autism means different things to different people. To some it means a need for life-long support. To others it is part of the varied tapestry of humanity. To all it means a need to foster a welcoming society with appropriate support and opportunities.